scholarly journals Identification of EMT-related high-risk stage II colorectal cancer and characterisation of metastasis-related genes

2020 ◽  
Vol 123 (3) ◽  
pp. 410-417 ◽  
Author(s):  
Kai Wang ◽  
Kai Song ◽  
Zhigang Ma ◽  
Yang Yao ◽  
Chao Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Gene Pair ◽  
Stage Ii ◽  
Related Gene ◽  
Prognostic Signature ◽  
Mesenchymal Transition ◽  
Relapse Risk ◽  
Gene Pairs ◽  
Stage Ii Colorectal Cancer

Abstract Background Our laboratory previously reported an individual-level prognostic signature for patients with stage II colorectal cancer (CRC). However, this signature was not applicable for RNA-sequencing datasets. In this study, we constructed a robust epithelial-to-mesenchymal transition (EMT)- related gene pair prognostic signature. Methods Based on EMT-related genes, metastasis-associated gene pairs were identified between metastatic and non-metastatic samples. Then, we selected prognosis-associated gene pairs, which were significantly correlated with disease-free survival of stage II CRC using multivariate Cox regression model, as the EMT-related prognosis signature. Results An EMT-related signature composed of fifty-one gene pairs (51-GPS) for prediction-relapse risk of patients with stage II CRC was developed, whose prognostic efficiency was validated in independent datasets. Moreover, 51-GPS achieved better predictive performance than other reported signatures, including a commercial signature Oncotype Dx colon cancer and an immune-related gene pair signature. Besides, EMT-related functional gene sets achieved high enrichment scores in high-risk samples. Especially, loss-of-function antisense approach showed that DEGs between the predicted two clusters were metastasis-related. Conclusions The EMT-related gene pair signature can identify the high relapse-risk patients with stage II CRC, which can facilitate individualised management of patients.

Identifying an immune-related gene-pair for prognosis prediction of metastatic colorectal cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15565-e15565
Author(s):  
Qiqi Zhu ◽  
Du Cai ◽  
Wei Wang ◽  
Min-Er Zhong ◽  
Dejun Fan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Prognostic Value ◽  
Validation Cohort ◽  
Risk Group ◽  
High Risk Group ◽  
Related Gene ◽  
Training Cohort ◽  
Gene Pairs ◽  
Immune Related Gene

e15565 Background: Few robust predictive biomarkers have been applied in clinical practice due to the heterogeneity of metastatic colorectal cancer (mCRC) . Using the gene pair method, the absolute expression value of genes can be converted into the relative order of genes, which can minimize the influence of the sequencing platform difference and batch effects, and improve the robustness of the model. The main objective of this study was to establish an immune-related gene pairs signature (IRGPs) and evaluate the impact of the IRGPs in predicting the prognosis in mCRC. Methods: A total of 205 mCRC patients containing overall survival (OS) information from the training cohort ( n = 119) and validation cohort ( n = 86) were enrolled in this study. LASSO algorithm was used to select prognosis related gene pairs. Univariate and multivariate analyses were used to validate the prognostic value of the IRGPs. Gene sets enrichment analysis (GSEA) and immune infiltration analysis were used to explore the underlying biological mechanism. Results: An IRGPs signature containing 22 gene pairs was constructed, which could significantly separate patients of the training cohort ( n = 119) and validation cohort ( n = 86) into the low-risk and high-risk group with different outcomes. Multivariate analysis with clinical factors confirmed the independent prognostic value of IRGPs that higher IRGPs was associated with worse prognosis (training cohort: hazard ratio (HR) = 10.54[4.99-22.32], P < 0.001; validation cohort: HR = 3.53[1.24-10.08], P = 0.012). GSEA showed that several metastasis and immune-related pathway including angiogenesis, TGF-β-signaling, epithelial-mesenchymal transition and inflammatory response were enriched in the high-risk group. Through further analysis of the immune factors, we found that the proportions of CD4+ memory T cell, regulatory T cell, and Myeloid dendritic cell were significantly higher in the low-risk group, while the infiltrations of the Macrophage (M0) and Neutrophil were significantly higher in the high-risk group. Conclusions: The IRGPs signature could predict the prognosis of mCRC patients. Further prospective validations are needed to confirm the clinical utility of IRGPs in the treatment decision.

Mucinous Adenocarcinoma as a High-risk Factor in Stage II Colorectal Cancer: A Propensity Score-matched Study from Japan

2020 ◽  
Vol 40 (3) ◽  
pp. 1651-1659 ◽  
Author(s):  
LIMING WANG ◽  
YASUMITSU HIRANO ◽  
GREGORY HENG ◽  
TOSHIMASA ISHII ◽  
HIROKA KONDO ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Factor ◽  
High Risk ◽  
Propensity Score ◽  
Mucinous Adenocarcinoma ◽  
Stage Ii ◽  
High Risk Factor ◽  
Stage Ii Colorectal Cancer ◽  
Matched Study

scholarly journals A rank-based transcriptional signature for predicting relapse risk of stage II colorectal cancer identified with proper data sources

Oncotarget ◽  
2016 ◽  
Vol 7 (14) ◽  
pp. 19060-19071 ◽  
Author(s):  
Wenyuan Zhao ◽  
Beibei Chen ◽  
Xin Guo ◽  
Ruiping Wang ◽  
Zhiqiang Chang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Data Sources ◽  
Stage Ii ◽  
Relapse Risk ◽  
Transcriptional Signature ◽  
Stage Ii Colorectal Cancer

scholarly journals Development and validation of an individualized immune-related gene pairs prognostic signature in papillary renal cell carcinoma

2020 ◽  
Author(s):  
Xianghong Zhou ◽  
Shi Qiu ◽  
Di Jin ◽  
Kun Jin ◽  
Xiaonan Zheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Risk ◽  
Risk Group ◽  
High Risk Group ◽  
Related Gene ◽  
Prognostic Signature ◽  
Gene Pairs ◽  
Immune Related Gene ◽  
Immune Related Genes

Abstract Background: Papillary renal carcinoma (PRCC) is one of the important subtypes of kidney cancer, with a high degree of heterogeneity. At present, there is still a lack of robust and accurate biomarkers for the diagnosis, prognosis and treatment selection of PRCC. Considering the important role of tumor immunity in PRCC, we aim to construct a signature based on immune-related gene pairs (IRGPs) to estimate the prognostic of patients with PRCC.Methods: We obtained gene expression profiling and clinical information of patients with PRCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), which were divided into discovery and validation cohorts, respectively. The immune-related genes in the samples were used to construct gene pairs, and the immune-related genes pairs (IRGPs) with robust impact for overall survival (OS) were screened out to construct the signature by univariate analysis, multivariate Cox analysis, and least absolute shrinkage and selection operator (Lasso) analysis. Then we verified the prognostic role of the signature, and assessed the relationship between this signature with tumor immune infiltration and functional pathways.Results: A total of 315 patients were included in our study, and divided to discovery (n=287) and validation (n=28) cohorts. Finally, we selected 14 IRGPs with a panel of 22 unique genes to construct the prognostic signature. According to the signature, we stratified patients into high-risk group and low-risk group. In both discovery and validation cohorts, the results of Kaplan-Meier analysis showed that there were significant differences in OS between the two groups (p<0.001). Combined with multiple clinical pathological factors, the results of multivariate analyses confirmed that this signature was an independent predictor of OS (HR, 3.548; 95%CI, 2.096−6.006; p<0.001). The results of immune infiltration analysis demonstrated that the abundance of multiple tumor-infiltration lymphocytes such as CD8+ T cells, Tregs, and T follicular cell helper were significantly higher in the high-risk group. Functional analysis showed that multiple immune-related signaling pathways were enriched in the high-risk group.Conclusions: We successfully established an individualized prognostic immune-related gene pairs signature, which can accurately and independently predict the OS of patients with PRCC.

Immunological nomograms predicting prognosis and guiding adjuvant chemotherapy in stage II colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 499-499
Author(s):  
Junjie Peng ◽  
Yaqi Li ◽  
Yang Feng
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Risk Groups ◽  
High Risk Group ◽  
Stage Ii ◽  
Stage Ii Colorectal Cancer

499 Background: The type, abundance, and location of tumor-infiltrating lymphocytes (TILs) have been associated with prognosis in colorectal cancer. The objective of this study was to assess the prognostic role of TILs and develop a nomogram for accurate prognostication of stage II colorectal cancer. Methods: Immunohistochemistry was conducted to assess the densities of intraepithelial and stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs, and to estimate PD-L1 expression in tumor cells for 168 patients with stage II colorectal cancer. The prognostic roles of these features were evaluated using COX regression model, and nomograms were established to stratify patients into low and high-risk groups and compare the benefit from adjuvant chemotherapy. Results: In univariate analysis, patients with high intraepithelial or stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs were associated significantly with better relapse-free survival (RFS) and overall survival (OS), except for stromal CD45RO+ TILs, whereas PD-L1 expression wasn't associated with RFS or OS. In multivariate analysis, patients with high intraepithelial CD3+ and stromal FOXP3+ TILs were associated with better RFS (p < 0.001 and p = 0.032, respectively), while only stromal FOXP3+ TILs was an independent prognostic factor for OS (p = 0.031). The nomograms were well calibrated and showed a c-index of 0.751 and 0.757 for RFS and OS, respectively. After stratifying into low and high-risk groups, the high-risk group exhibited a better OS from adjuvant chemotherapy (3-year OS of 81.9% v 34.3%, p = 0.006). Conclusions: These results may help improve the prognostication of stage II colorectal cancer and identify a high-risk subset of patients who appeared to benefit from adjuvant chemotherapy.

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